Randomized controlled trial of the Breast Cancer Recovery Program for women with breast cancer-related lymphedema.

Evidence-based exercise and relaxation recommendations for people with breast cancer-related lymphedema (BCRL) are needed. We report a randomized controlled study of one program, designed to achieve synergistic improvements in physical and emotional BCRL symptoms. People in the treatment group received an exercise and relaxation program, The Breast Cancer Recovery Program (N=16). The control participants (N=16) continued with health professionals' recommendations. Participants were tested at entry, 2.5 weeks, 5 weeks, and 3 months. Treatment group participants, compared with control participants, demonstrated significant treatment effects for improved bioimpedance z, arm flexibility, quality of life, mood at 3 months, and weight loss. Adherence was high for this safe and effective program, which improved lymphedema physical and emotional symptoms.

Molecular neurodevelopment: an in vivo 31P-1H MRSI study.

Synaptic development and elimination are normal neurodevelopmental processes, which if altered could contribute to various neuropsychiatric disorders. 31P-1H magnetic resonance spectroscopic imaging (MRSI) and structural magnetic resonance imaging (MRI) exams were conducted on 105 healthy children ages 6-18 years old to identify neuromolecular indices of synaptic development and elimination. Over the age range studied, age-related changes in high-energy phosphate (phosphocreatine), membrane phospholipid metabolism (precursors and breakdown products), and percent gray matter volume were found. These neuromolecular and structural indices of synaptic development and elimination are associated with development of several cognitive domains. Monitoring of these molecular markers is essential for devising treatment strategies for neurodevelopmental disorders.

Effect of intraperitoneal acetyl-L-carnitine (ALCAR) on anxiety-like behaviours in rats.

Acetyl-L-carnitine (ALCAR) is an acetyl derivative of carnitine, an endogenous molecule synthesized in vivo and supplemented by diet (mainly via meat and dairy products). Several parallel, double-blind, placebo-controlled studies have demonstrated that ALCAR treatment produces beneficial effects in geriatric depression. Since most antidepressants also have anti-anxiety effects we examined whether ALCAR shows anti-anxiety effects in a rat model of anxiety. Compared to a saline-injected control group, chronic administration of ALCAR at doses of 10 and 100 mg/kg (tested 24 h after the last dose administration) showed no effects, whereas doses of 50 and 75 mg/kg significantly reduced anxiety-like behaviours in the elevated plus-maze. Acute ALCAR (100 mg/kg), on the other hand (tested 6 h after administration), demonstrated anxiogenic effects. Our data suggest that chronic ALCAR administration may produce an inverted U-shaped curve of dose-dependent changes in anxiety-like behaviour. The precise mechanism by which ALCAR decreases anxiety-like behaviour after peripheral administration remains to be determined.

Interactions of Abeta(1-40) with glycerophosphocholine and intact erythrocyte membranes: fluorescence and circular dichroism studies.

Deposition of amyloid beta peptide in human brain in the form of senile plaques is a neuropathological hallmark of Alzheimer's disease (AD). Levels of a phospholipid breakdown product, glycerophosphocholine (GPC), also increase in AD brain. The effect of GPC on amyloid beta(1-40) peptide (Abeta) aggregation in PBS buffer was investigated by circular dichroism and fluoresence spectroscopy; interactions of Abeta and GPC with the intact erythrocyte membrane was examined by fluoresence spectroscopy. Fluorescamine labeled Abeta studies indicate GPC enhances Abeta aggregation. CD spectroscopy reveals that Abeta in the presence of GPC adopts 14% more beta-sheet structure than does Abeta alone. Fluorescamine anisotropy measurements show that GPC and Abeta interact in the phospholipid head-group region of the erythrocyte membrane. In summary, both soluble Abeta and GPC insert into the phospholipid head-group region of the membrane where they interact leading to beta-sheet formation in soluble Abeta which enhances Abeta aggregation.

31P-MRS study of acetyl-L-carnitine treatment in geriatric depression: preliminary results.

OBJECTIVE: This 12-week study of two elderly, depressed subjects investigated the effect of acetyl-L-carnitine (ALCAR) treatment on the Hamilton Depression Rating Scale (HDRS) and on measures of high-energy phosphate and membrane phospholipid metabolism. METHODS: Two mildly depressed (HDRS 15-20), non-demented male subjects 70 and 80 years old were compared with six non-demented controls (all males, mean age of 73.6 +/- 3.6 years). High-energy and membrane phospholipid metabolites were measured by phosphorus magnetic resonance spectroscopic imaging (31P MRSI) analysis. HDRS and 31P MRSI measurements were taken at entry, 6 and 12 weeks for the depressed subjects. RESULTS: 31P MRSI analysis revealed elevated levels of phosphomonesters [PME(s - tau(c))] in the prefrontal region of these mildly depressed subjects, which decreased with ALCAR treatment and showed a trend for correlation of the PME(s - tau(c)) levels with HDRS. ALCAR treatment also resulted in increasing levels of the prefrontal phosphocreatine (PCr), which correlated with HDRS. CONCLUSIONS: In the prefrontal region, the mildly depressed subjects compared with controls had elevated PME(s - tau(c)) levels which normalized after 12 weeks of ALCAR and increased PCr levels after ALCAR treatment. These preliminary findings suggest further studies are warranted.

Psychosis in Alzheimer disease: postmortem magnetic resonance spectroscopy evidence of excess neuronal and membrane phospholipid pathology.

BACKGROUND: The presence of psychotic symptoms in Alzheimer Disease subjects (AD+psychosis, AD+P) is a marker for a phenotype characterized by more severe cognitive impairment and a more rapidly deteriorating course. Although AD+P has been inconsistently associated with more severe neuropathology, no prior studies have examined measures of neuronal and synaptic integrity. OBJECTIVE: To determine whether AD+P is associated with evidence of disrupted neuronal and synaptic integrity, as indicated by magnetic resonance spectroscopy (MRS) measurement of N-acetyl-L-aspartate and the membrane breakdown products, glycerophosphocholine and glycerophosphoethanolamine. METHODS: 31P and 1H MRS studies of perchloric acid extract from postmortem brain of AD subjects with and without a history of psychotic symptoms. All subjects were characterized for the presence of comorbid cortical Lewy body pathology and for history of neuroleptic use. Brain tissue from dorsolateral prefrontal, superior temporal, inferior parietal, and occipital cortex, amygdala, and cerebellum were examined in all subjects. Statistical analysis accounted for correlated observations across brain regions within-subjects. RESULTS: AD+P subjects demonstrated significant elevations of glycerophosphoethanolamine and significant reductions of N-acetyl-L-aspartate. Between group differences were greatest in neocortical brain regions. CONCLUSION: Excess impairment of neocortical neuronal and synaptic integrity may provide the structural substrate underlying AD+P. Confirmation of these findings using in vivo MRS measures is indicated.

Acetyl-l-carnitine as a possible therapy for Alzheimer's disease.

Alterations have been demonstrated in membrane phospholipid metabolism in Alzheimer's disease. Alterations in membrane phospholipid metabolite levels have been observed by 31P magnetic resonance spectroscopy 4 years before onset of cognitive changes. Implications of phospholipid membrane changes in Alzheimer's disease are presented. Augmentation of brain levels of acetyl-l-carnitine, an endogenous molecule, may help to reverse membrane phospholipid changes in Alzheimer's disease. Neurobiological effects of acetyl-l-carnitine and potential molecular mechanisms of acetyl-l-carnitine activity are reviewed. Clinical trials of acetyl-l-carnitine indicate that it is well-tolerated and may be effective in younger Alzheimer's disease patients and may be an effective adjuvant treatment. Acetyl-l-carnitine may especially benefit those Alzheimer's disease patients with depressive disorders.